Contribution of the inflammasome to the inflammatory response in Alzheimer’s disease after traumatic brain injury 2706

Abstract Description Individuals having a genetic predisposition towards AD present worse outcomes after TBI. However, the mechanism by which TBI contributes to AD pathology is yet to be understood. Here we aimed to understand the contribution of the inflammasome to the pathology of AD in the 3xTg model of AD along with their respective B6129SF2 (WT) controls in light of having had a TBI. AD and WT mice underwent sham surgery or TBI and were sacrificed at acute and chronic time points up to 3-months post-TBI. Cortical lysates were collected and probed for inflammasome signaling via immunoblotting and ECLIA. Brain sections were used for lesion volume and immunohistochemistry of the inflammasome. Our findings indicate an acute increase of the inflammasome after TBI that was higher in 3xTg-TBI mice compared to WT-TBI. In addition, inflammasome activation was higher in 3xTg-TBI mice than in 3xTg-sham. Moreover, the effects of TBI on inflammasome activation persisted in the chronic phase in 3xTg-TBI mice compared to WT-TBI. 3xTg-TBI mice had significant loss of total cortical and hippocampal volume compared to WT-TBI mice. Together, these findings indicate that having a genetic predisposition towards AD and suffering from a TBI results in an exacerbated inflammatory response that is, in part, mediated by the inflammasome, and that this genetic predisposition results in a more prolonged inflammatory response after TBI than those that did not have AD but also had a TBI. Funding Sources This research was funded by an RF1 grant from the NIH/NINDS/NIA (1RF1NS125578-01) to WDD and JPdRV. Topic Categories Neuroimmunology (NEUR)